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971.
Hao Zhou Tao Deng Ran Tao Wenjun Li 《Journal of biomolecular structure & dynamics》2018,36(8):1966-1978
Three series of novel urushiol derivatives were designed by introducing a hydroxamic acid moiety into the tail of an alkyl side chain and substituents with differing electronic properties or steric bulk onto the benzene ring and alkyl side chain. The compounds’ binding affinity toward HDAC8 was screened by Glide docking. The highest-scoring compounds were processed further with molecular docking, MD simulations, and binding free energy studies to analyze the binding modes and mechanisms. Ten compounds had Glide scores of ?8.2 to ?10.2, which revealed that introducing hydroxy, carbonyl, amino, or methyl ether groups into the alkyl side chain or addition of –F, –Cl, sulfonamide, benzamido, amino, or hydroxy substituents on the benzene ring could significantly increase binding affinity. Molecular docking studies revealed that zinc ion coordination, hydrogen bonding, and hydrophobic interactions contributed to the high calculated binding affinities of these compounds toward HDAC8. MD simulations and binding free energy studies showed that all complexes possessed good stability, as characterized by low RMSDs, low RMSFs of residues, moderate hydrogen bonding and zinc ion coordination and low values of binding free energies. Hie147, Tyr121, Phe175, Hip110, Phe119, Tyr273, Lys21, Gly118, Gln230, Leu122, Gly269, and Gly107 contributed favorably to the binding; and Van der Waals and electrostatic interactions provided major contributions to the stability of these complexes. These results show the potential of urushiol derivatives as HDAC8 binding lead compounds, which have great therapeutic potential in the treatment of various malignancies, neurological disorders, and human parasitic diseases. 相似文献
972.
Varsha Bhavnani Swarnendu Kaviraj Priyabrata Panigrahi C.G. Suresh SuneelShekar Yapara 《Journal of biomolecular structure & dynamics》2018,36(11):2845-2861
The eIF2α kinase activity of the heme-regulated inhibitor (HRI) is regulated by heme which makes it a unique member of the family of eIF2α kinases. Since heme concentrations create an equilibrium for the kinase to be active/inactive, it becomes important to study the heme binding effects upon the kinase and understanding its mechanism of functionality. In the present study, we report the thermostability achieved by the catalytic kinase domain of HRI (HRI.CKD) upon ligand (heme) binding. Our CD data demonstrates that the HRI.CKD retains its secondary structure at higher temperatures when it is in ligand bound state. HRI.CKD when incubated with hemin loses its monomeric state and attains a higher order oligomeric form resulting in its stability. The HRI.CKD fails to refold into its native conformation upon mutation of H377A/H381A, thereby confirming the necessity of these His residues for correct folding, stability, and activity of the kinase. Though our in silico study demonstrated these His being the ligand binding sites in the kinase insert region, the spectra-based study did not show significant difference in heme affinity for the wild type and His mutant HRI.CKD. 相似文献
973.
Pedro Jimenez‐Sandoval Ezequiel A. Madrigal‐Carrillo Hugo A. Santamaría‐Suárez Daniel Maturana Itzel Rentería‐González Claudia G. Benitez‐Cardoza Alfredo Torres‐Larios Luis G. Brieba 《Proteins》2018,86(7):802-812
Antibodies recognize protein targets with great affinity and specificity. However, posttranslational modifications and the presence of intrinsic disulfide‐bonds pose difficulties for their industrial use. The immunoglobulin fold is one of the most ubiquitous folds in nature and it is found in many proteins besides antibodies. An example of a protein family with an immunoglobulin‐like fold is the Cysteine Protease Inhibitors (ICP) family I42 of the MEROPs database for protease and protease inhibitors. Members of this protein family are thermostable and do not present internal disulfide bonds. Crystal structures of several ICPs indicate that they resemble the Ig‐like domain of the human T cell co‐receptor CD8α As ICPs present 2 flexible recognition loops that vary accordingly to their targeted protease, we hypothesize that members of this protein family would be ideal to design peptide aptamers that mimic protein‐protein interactions. Herein, we use an ICP variant from Entamoeba histolytica (EhICP1) to mimic the interaction between p53 and MDM2. We found that a 13 amino‐acid peptide derived from p53 can be introduced in 2 variable loops (DE, FG) but not the third (BC). Chimeric EhICP1‐p53 form a stable complex with MDM2 at a micromolar range. Crystal structure of the EhICP1‐p53(FG)‐loop variant in complex with MDM2 reveals a swapping subdomain between 2 chimeric molecules, however, the p53 peptide interacts with MDM2 as in previous crystal structures. The structural details of the EhICP1‐p53(FG) interaction with MDM2 resemble the interaction between an antibody and MDM2. 相似文献
974.
975.
Manabu Fukui Jungin Suh Yoshitaka Yonezawa Yoshikuni Urushigawa 《Ecological Research》1997,12(2):201-209
To clarify the anaerobic microbial interactions in the process of carbon mineralization in marine eutrophic environments,
the microbial sulfate reduction and methane production rates were examined in coastal marine sediments of Ise Bay, Japan,
in autumn 1990. Sulfate reduction rates (51–210 nmol ml−1 day−1 at 24°C) were much higher than the methane production ones (<1.78 nmol ml−1 day−1) in the surface sediments (top 2 cm) at the six stations surveyed (water depth: 10.7–23.3 m). Substrates for sulfate-reducing
bacteria (SRB) were estimated after the addition of a specific inhibitor for SRB (20 mmol l−1 molybdate) into the sediment slurry, from the substrate accumulation rates. In the presence of the inhibitor, sulfate reduction
was completely stopped and volatile fatty acids (mainly acetate) were accumulated, although hydrogen was not. Methane production
occurred markedly accompanied by consumption of the accumulated acetate from the third day after the addition of molybdate.
The maximum rate of methane production was 1.2–1.9 μmol ml−1 day−1, which was similar to those in highly polluted freshwater sediments such as the Tama River, Tokyo, Japan. These results show
that acetate is a common major substrate for sulfate reduction and methane production, and SRB competitively inhibit potential
acetoclastic methanogenesis in coastal sediments. Methanogens may potentially inhabit the sediments at low levels of population
density and activity. 相似文献
976.
By means of a Sephadex G-50 column and anionic exchange HPLC a cerebral cortex soluble fraction (II-E) which highly inhibits neuronal Na+-K+-ATPase activity has been previously obtained. Herein, II-E properties are compared with those of the cardenolide ouabain, the selective and specific Na+, K+-ATPase inhibitor. It was observed that alkali treatment destroyed II-E but not ouabain inhibitory activity. II-E presented a maximal absorbance at 265 nm both at pH 7 and pH 2 which diminished at pH 10. Ouabain showed a maximum at 220 nm which was not altered by alkalinization. II-E was not retained in a C-18 column, indicating its hydrophilic nature, whereas ouabain presented a 26-min retention time in reverse phase HPLC. Therefore, it is concluded that the inhibitory factor present in II-E is structurally different to ouabain. 相似文献
977.
978.
Eun-Gyu No Richard B. Flagler Martha A. Swize John Cairney Ronald J. Newton 《Physiologia plantarum》1997,100(1):137-146
Ozone effects on plant water relations have been reported to be similar to those of water-deficit. The objective was to identify ozone-inducible (OI) clones from Atriplex canescens (saltbush) and determine if they were also responsive to water-deficit as well as SO2 . cDNA clones derived from four different polyA RNAs which accumulate in 8-month-old shrub leaves exposed to ozone (0.2 μl I−1 , 6 h day−1 , 7 days) were isolated by differential screening, analyzed by northern blots, sequenced, and gene product homologies with other plant genes were determined. Clone OI12A-3 has homology with wound-inducible proteinase inhibitors, whereas clone OI8–3 protein is homologous to thiol proteases. Clones OI2–2 and OI14–3 putatively code for glycine-rich proteins with repeated motifs (Gly-Gly-Gly-Tyr-Gly-His)n and putative cell-wall-targeting signal peptides. Clone OI2–2 and particularly clone OI14–3 were also induced by both SO2 and water-deficit. These data indicate that woody plant genes associated with cell wall protein production and whose expression is induced by several stress factors may be responding to common oxidative stress pathways. 相似文献
979.
M. Fatima Grossi de Sa T. Erik Mirkov Masao Ishimoto Gabriella Colucci Kaye S. Bateman Maarten J. Chrispeels 《Planta》1997,203(3):295-303
Cultivated varieties of the common bean (Phaseolus vulgaris L.) contain an α-amylase inhibitor (αAI-1) that inhibits porcine pancreatic α-amylase (PPA; EC 3.2.1.1) and the amylases
of certain seed weevils, but not that of the Mexican bean weevil, Zabrotes subfasciatus. A variant of αAI-1, called αAI-2, is found in certain arcelin-containing wild accessions of the common bean. The variant
αAI-2 inhibits Z. subfasciatus α-amylase (ZSA), but not PPA. We purified αAI-2 and studied its interaction with ZSA. The formation of the αAI-2-ZSA complex
is time-dependent and occurs maximally at pH 5.0 or below. When a previously isolated cDNA assumed to encode αAI-2 was expressed
in transgenic tobacco seeds, the seeds contained inhibitory activity toward ZSA but not toward PPA, confirming that the cDNA
encodes αAI-2. The inhibitors αAI-1 and αAI-2 share 78% sequence identity at the amino acid level and they differ in an important
region that is part of the site where the enzyme binds the inhibitor. The swap of a tripeptide in this region was not sufficient
to change the specificity of the two inhibitors towards their respective enzymes. The three-dimensional structure of the αAI-1/PPA
complex has just been solved and we recently obtained the derived amino acid sequence of ZSA. This additional information
allows us to discuss the results described here in the framework of the amino acid residues of both proteins involved in the
formation of the enzyme-inhibitor complex and to pinpoint the amino acids responsible for the specificity of the interaction.
Received: 14 April 1997 / Accepted: 10 May 1997 相似文献
980.
Hidemitsu Kitamura Nobuko Takemoto Morimichi Mizuno Yoshinori Kuboki Nobuo Sakairi Norio Nishi 《International journal of biological macromolecules》1997,21(4):337-340
Phase-contrast and fluorescence microscopic observation showed that DNA added in the cell-culture medium for fibroblasts localized just on the surface of fibroblasts. The DNA bound to fibroblasts was found to be eluted by treating with collagenase. The suppression for the proliferation of fibroblasts by external DNA was confirmed with microscopic observation for the cells cultured in the presence and absence of DNA. Proliferation of the cells decreased from 412 to 155% by the addition of DNA. These results indicate that DNA has an affinity for collagen, the most major extracellular-matrix produced by fibroblasts, and suppresses the growth of fibroblasts. 相似文献